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KDELR1是胶质瘤的独立预后预测指标并与免疫相关。

KDELR1 Is an Independent Prognostic Predictor and Correlates With Immunity in Glioma.

作者信息

Yuan Yifan, Yang Biao, Qi Zengxin, Han Zhenyuan, Cai Jiajun, Song Jianping

机构信息

Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.

National Center for Neurological Disorders, Shanghai, China.

出版信息

Front Oncol. 2022 Jun 23;12:783721. doi: 10.3389/fonc.2022.783721. eCollection 2022.

Abstract

BACKGROUND

Gliomas are the most malignant central nervous system tumors. With the development of sequencing technology, more potential biomarkers related to the treatment, prognosis, and molecular classification of glioma have been identified. Here, we intend to investigate the potential biological function and clinical value of a new biomarker in glioma.

METHODS

KDELR1 expression data and the corresponding clinical information were downloaded from public databases and then preprocessed using R language. Correlation, Kaplan-Meier survival, and Cox regression analyses were performed to explore the clinical significance of KDELR1 in glioma patients. Furthermore, the immune infiltration and microenvironment parameters were evaluated TIMER and CIBERSORT. Immunohistochemistry was conducted to confirm the KDELR1 expression and its correlation with immunity infiltration and prognosis.

RESULTS

KDELR1 was upregulated in glioma samples compared with normal brain tissues, and its expression was significantly correlated with age, the World Health Organization (WHO) grade, recurrence, necrosis, microvascular proliferation, molecular classification, isocitrate dehydrogenase (IDH) mutation, and 1p/19q codeletion status. In addition, survival analysis showed that glioma patients with KDELR1 overexpression had shorter overall survival (OS) and disease-free survival times, and Cox regression analysis revealed that KDELR1 acted as an independent prognostic factor of OS in glioma patients. Gene set enrichment analysis indicated a significant enrichment of metabolism-associated pathways. KDELR1 expression was positively associated with immune infiltration (including infiltration by CD8+ T cells, CD4+ T cells, macrophages, and so on) and microenvironment parameters (including stromal, immune, and ESTIMATE scores) in gliomas. The expression of KDELR1 and its correlation with the tumor grade and prognosis were confirmed by immunohistochemistry in clinical samples (n = 119, P < 0.05).

CONCLUSIONS

Taken together, these findings suggest that KDELR1 is correlated with the tumor grade, molecular classifications, and immune infiltration; highlighting that KDELR1 is a novel and promising biomarker for molecular classification, treatment, and prognostic assessment may further indicate the treating effect of immune therapy.

摘要

背景

胶质瘤是最恶性的中枢神经系统肿瘤。随着测序技术的发展,已鉴定出更多与胶质瘤治疗、预后和分子分类相关的潜在生物标志物。在此,我们旨在研究一种新的生物标志物在胶质瘤中的潜在生物学功能和临床价值。

方法

从公共数据库下载KDELR1表达数据及相应临床信息,然后用R语言进行预处理。进行相关性分析、Kaplan-Meier生存分析和Cox回归分析,以探讨KDELR1在胶质瘤患者中的临床意义。此外,使用TIMER和CIBERSORT评估免疫浸润和微环境参数。进行免疫组织化学以确认KDELR1表达及其与免疫浸润和预后的相关性。

结果

与正常脑组织相比,胶质瘤样本中KDELR1表达上调,其表达与年龄、世界卫生组织(WHO)分级、复发、坏死、微血管增生、分子分类、异柠檬酸脱氢酶(IDH)突变和1p/19q共缺失状态显著相关。此外,生存分析表明,KDELR1过表达的胶质瘤患者总生存期(OS)和无病生存期较短,Cox回归分析显示KDELR1是胶质瘤患者OS的独立预后因素。基因集富集分析表明代谢相关通路显著富集。KDELR1表达与胶质瘤中的免疫浸润(包括CD8+T细胞、CD4+T细胞、巨噬细胞等的浸润)和微环境参数(包括基质、免疫和ESTIMATE评分)呈正相关。临床样本(n = 119,P < 0.05)的免疫组织化学证实了KDELR1的表达及其与肿瘤分级和预后的相关性。

结论

综上所述,这些发现表明KDELR1与肿瘤分级、分子分类和免疫浸润相关;突出表明KDELR1是一种用于分子分类、治疗和预后评估的新型且有前景的生物标志物,可能进一步指示免疫治疗的疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27d3/9263977/50c83a8c043f/fonc-12-783721-g001.jpg

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